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Pilot Study of Peak Plasma Concentration After High‐Dose Oral Montelukast in Children With Acute Asthma Exacerbations
Author(s) -
Arnold Donald H.,
Van Driest Sara L.,
Reiss Theodore F.,
King Jennifer C.,
Akers Wendell S.
Publication year - 2021
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1738
Subject(s) - montelukast , medicine , asthma , adverse effect , inhalation , anesthesia , gastroenterology , pharmacology
Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti‐inflammatory properties, not all inflammatory pathways are responsive to systemic corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non‐responsiveness. Montelukast is a potent LT‐receptor antagonist, and an intravenous preparation caused rapid, sustained improvement of acute asthma exacerbations in adults. We hypothesized that a 30‐mg dose of oral montelukast achieves peak plasma concentrations (C max ), comparable to the intravenous preparation (1700 ng/mL) and would be well tolerated in 15 children aged 5 to 12 years with acute asthma exacerbations. After administration of montelukast chewable tablets, blood samples were collected at 0, 15, 30, 45, 60, 120, 180, and 240 minutes. Plasma was separated and frozen at −80°C until analysis for montelukast concentration using liquid chromatography‐ tandem mass spectrometry. Median time to C max (t max ) was 3.0 hours. Six participants (40%) achieved C max of 1700 ng/mL or higher. However, there was high interindividual variability in peak plasma concentration (median C max of 1378 ng/mL; range, 16‐4895 ng/mL). No participant had side effects or adverse events. Plasma concentrations from this pilot study support the design of a weight‐based dose‐finding study aimed at selecting an optimal dose for future clinical trials to assess the efficacy of high‐dose oral montelukast in children with moderate to severe asthma exacerbations.